JP2008546834A - Parenteral selenomethionine for the production of selenium rich foods - Google Patents

Abstract

A formulation for parenteral administration comprising selenomethionine and one or more oil-based vehicles. This formulation is used to increase selenium concentration in one or more of animal blood, milk and meat. These products (ie milk and meat) and the formulation itself are used to meet selenium nutritional requirements for growth and health in selenium deficient animals.

Description

  The present invention relates to parenteral selenomethionine for the production of selenium rich foods. More particularly, the invention relates to a formulation comprising selenomethionine and a method of using the formulation to significantly increase selenium concentrations in animal-derived milk, meat or both.

[The nutritional role and value of selenium in the diet]
Knowledgeable consumers are increasingly demanding foods that have advantages over simple nutrition, suit lifestyles, individual preferences, and meet specific dietary requirements. This has prompted interest in foods that contain high concentrations of vitamins and minerals. Nutritional adjustments to produce such foods can be achieved by several approaches, but it is preferable to produce the desired changes on the farm and improve the food directly without subsequent manipulation. It is.

  One mineral of interest is selenium. Selenium is a trace element that is generally essential for growth and health in humans and animals. In the body, selenium is incorporated into proteins and produces selenoproteins. Selenoproteins are active in cell detoxification, cycling in the redox cycle and antioxidant defense against cell damage by free radicals. Free radicals are natural by-products of oxygen metabolism that contribute to the development of chronic diseases such as cancer and heart disease. Other selenoproteins regulate thyroid function and play a role in the immune system. Except in extreme cases, selenium deficiency itself does not cause disease, but selenium deficiency has a greater impact on the body against diseases caused by other nutritional, biochemical or infectious stresses. May be easier to receive.

  As with all essential minerals, the source of selenium is the diet. Standards in New Zealand and others provide selenium dietary intake standards (RDI) or recommended daily requirements (RDA) for healthy consumers of various ages. The RDI for New Zealand and Australia was established by the Australian National Health and Medical Research Council and is currently as follows:

Those skilled in the art will appreciate that the above information is provided as an example only, as differences exist in RDI / RDA concentrations in various countries.
As a result of national geology that determines the mineral content of the soil that affects the absorption of minerals by the crop and ultimately the selenium content of the food grown there, New Zealanders' selenium nutritional status is There is a tendency to be less than recommended by the World Health Organization. In the UK, recent changes in agriculture and import practices have also caused a decline in the selenium nutritional status of the general population.

  People who have a well-balanced and rich diet are usually able to meet their minimum intake requirements. However, old habits, diets or cultural practices that limit diverse food choices can severely limit the intake of good selenium sources. Therefore, many consumers are seeking a way to increase their selenium intake with nutritional supplements, which are often based on tablets, but more often by taking fortified foods.

Meat and milk from New Zealand livestock naturally contain selenium, albeit at low concentrations that reflect the composition of pasture diets. Normal selenium concentrations are 50 μg / kg (range 30-85 μg / kg) for fresh red beef or lamb (note 1) and 2-11 μg / liter for whole milk (note 2). The contribution of a 100 g or 100 ml intake to “typical” meat or milk to human daily selenium requirements is 1-6% and 1-20% for adults and infants, respectively. It is clear that higher concentrations of selenium increase the benefits of food intakes below 100 g.
Note 1: West Jay. (West J.), “Collecting of Nutritional Data on New Zealand Beef and Lamb in Domestic and Export Transactions (Compilation of
nutritious data for New Zealand beef and lambs in domestic and export trade ”, Project 96MZ 64 / 4.3, New Zealand Meat Research and Development Conference, New Zealand .
Note 2: Grace ND, Ankenbauer K, Alexander AM, Merchant RM, “Blood selenium or glutathione peroxidase activity and milk selenium concentration in New Zealand dairy cattle. (Relationship between blood selenium contention or glutatione peroxidase activity, and the milk selenium concentrations in the New Zealand journal) Winding, p. 24-28.

  In those foods (and major cereals), selenium exists primarily as a “selenomethionine” in the form of an organic chemical that is an analogue of the amino acid methionine. Selenomethionine is incorporated into body proteins instead of methionine, thus acting as a selenium reservoir in organs and tissues. Food-derived selenomethionine is considered to have high bioavailability in that it is well absorbed and utilized.

[Improvement of food nutrition by enriching selenium content]
It is possible to produce fortified foods by adding nutrients such as selenium exogenously (ie at the factory after harvest) or by growing excess selenium into the food endogenously before harvesting or slaughtering. is there. The advantage of the latter is that selenium is incorporated into the food in its natural chemical form and delivered to consumers without additives, avoiding post-harvest processing or concentration steps.

  One known method for endogenously enriching the selenium content of ruminant milk is to add selenium or selenomethionine to the animal feed, as described, for example, in US Pat. It depends. The feed additive also includes two inorganic forms of selenium salt, sodium selenite and sodium selenate. At least Patent Documents 4 to 6 describe examples of sodium selenite feed supplements.

An alternative way to increase the selenium concentration in animals and the resulting meat or milk is to administer selenium supplements by subcutaneous or intramuscular injection. Parenteral administration refers to taking the body into the body in ways other than through the digestive tract, but this has several obvious advantages over a dietary feed source, such as: To do.
• Treatment by injection is suitable for livestock that are grazed primarily in open ranches and usually not given any supplements (eg in New Zealand).
The cost of producing and administering an injection formulation can be lower than the cost of producing and feeding a dietary supplement.
The amount of selenium administered can be precisely controlled by injection, but the amount of selenium administered orally is less likely due to variations in feed manufacturers and in the amount eaten by various animals. Is accurate.
When administering selenium only to selected ones in a group, it is not necessary to separate the animals to be treated or adjust their diet in any way different from that for other animals, Injection is easier to handle than oral administration.
• Selenium doses by injection are lower because selenium is not lost due to feed waste or insufficient animal absorption. This reduces the amount of selenium that can be lost to the ground and leach into the water supply, which can be advantageous when there are environmental limitations.

  There are many injectable selenium supplements on the market, none of them “free of selenomethionine”. Among these selenium adjuvants is Deposel® from Novartis. Deposel is a blend of finely divided particles of “barium selenate” (inorganic selenium salt) that is injected subcutaneously into livestock animals and provides a long-term reservoir of selenium at the site of injection. Deposel is registered for use in sheep and cattle for the treatment and prevention of selenium deficiency. Its purpose is to maintain animal health, and no effect on selenium content in meat or milk is claimed.

  In New Zealand, more than 15 other injectable selenium supplements are registered as “parenteral nutrients”. They are all veterinary therapeutics containing the mineral “sodium selenite” or “sodium selenate”, none of which is claimed to have an effect on meat or milk composition. Patent Document 7 describes the intramuscular injection method of sodium selenite used for increasing milk production, however, it does not describe the change in selenium concentration in the produced milk.

We have tested injectable formulations of barium selenate and sodium selenate in livestock and the treatment increases the animal's selenium status (ie, blood selenium concentration), but the animal's milk or We found that almost no selenium moved to the meat. These foods are not sufficiently enriched for direct use as functional foods or fortified foods for human consumption without further processing such as a concentration step. One study (Note 1) conducted by the inventors used a single subcutaneous injection of barium selenate to increase the blood state of selenium in animals. This treatment only increased the selenium concentration of milk to total milk secretion (selenium / milk 6-11 μg / liter).
Note 1: Grace ND, Lee J, Mills AR, Death AF, “Effect of Se status on milk Se concentration in dairy cows
on milk Se concentrations in daily cows ", NZ Journal of Agricultural Research, 1997, 40, p. 75-78.

The second publication (Note 2) describes the amount of selenium in animal products, including changes in grass selenium intake (feed manipulation) or the use of long-acting animal injections or oral rumen boluses. A method of changing is allowed. This article also shows the use of injections containing an obvious chemical form of organic selenium to enrich the selenium content of meat. There is no mention of a formulation used to increase the selenium content of meat.
Note 2: Knowles SO, et al., “Additional Nutritional Value for meat and milk derived from pasture-fed livestock (Adding Nutritional Value)
to Meat and Milk from Paste-fed Livestock ", NZ Veterinary Journal, 2004, Vol. 52, pp.342-351.
Taiwan Patent Application No. TW0565432B Specification Chinese Patent Application No. CN1094899A Chinese Patent Application No. CN1217153A Chinese Patent Application No. CN1455284A Specification Chinese Patent Application No. CN1439284A Chinese Patent Application No. CN1455283A Specification Russian patent application RU2222192C2 specification

  Since parenteral administration of selenium to livestock has obvious advantages over a dietary supplemented feed source (see above black and white symbols), therefore, for example, as a supplement to human consumer dietary intake and It would be advantageous to have an injectable formulation and a suitable method for its administration that is used to increase significantly the selenium concentration in milk or meat for the benefit.

  The present invention aims to address the above-mentioned problems or at least generally provide useful options.

[Compound]
In one aspect of the invention, a formulation for parenteral administration is provided. The formulation includes selenomethionine and one or more oil-based vehicles.

As used herein, the term “parenteral” refers to taking something into the body, ie, administering, other than through the digestive tract, such as by subcutaneous injection or intramuscular injection.
As used herein, selenomethionine has a chemical structure of the following formula (I) representing a D-form, an L-enantiomer, or a racemic mixture thereof.

Preferably, selenomethionine is a finely divided particulate. More preferably, the particle size distribution of the selenomethionine form is 0.1-10 μm. Preferably, the concentration of selenomethionine in the formulation is in the range of about 25-100 g / L. More preferably, the concentration of selenomethionine is about 50 g / L. Preferably, the one or more oil-based vehicles are non-allergenic, flow thinly at room temperature, and are slowly degraded by oxidation. In one preferred embodiment, the viscosity of the oil-based vehicle is about 50-100 mPascal seconds at 23 ° C. In a preferred embodiment, the vehicle is vegetable oil. More preferably, the vehicle is selected from peanut oil, poppy seed oil and walnut oil. Most preferably, the vehicle is peanut oil or a similar oil with equal viscosity and temperature stability.

  Suitably the formulation also includes a suspending agent. The purpose of the suspending agent is long enough to allow the user to repeatedly remove the formulation from the container and administer the formulation to the animal when the formulation container is shaken. Is to make the formulation sufficiently thick so that the particles remain suspended in the vehicle.

  In a preferred embodiment, the suspending agent is beeswax, more preferably bleached beeswax. In our understanding, beeswax provides optimum suspendability and fluidity for the formulation by thickening the mixture and thus delaying the precipitation of selenomethionine particles from the solution. Preferably, the beeswax is added at a concentration in the range of about 5-50 g / L. More preferably, this concentration is about 15 g / L. In our experiments, this concentration range prevents the formulation from becoming too thick at low temperatures while minimizing the settling of the suspension.

Preferably, the suspending agent is a suitable pharmaceutical grade.
Preferably, sufficient suspending agent is added to the formulation such that the density of the formulation is about 0.92 g / ml when measured at 23 ° C.

[Method of administration]
In a further aspect of the invention, there is provided a method for increasing selenium concentration in an animal by parenteral administration of the formulation, substantially as described above.

In a further aspect of the present invention, there is provided a method of meeting selenium nutritional requirements for growth and health in deficient animals by parenteral administration of the formulation, substantially as described above.
In a further aspect of the invention, there is provided a method for increasing selenium concentration in milk, meat or both from animals by parenteral administration of the formulation, substantially as described above.

In a further aspect of the present invention, there is provided a method for increasing selenium concentration in milk, meat or both of animal origin by repeated parenteral administration of the formulation, substantially as described above.
Preferably, the formulation is administered repeatedly at different intervals. More preferably, the next administration of the formulation occurs about 50 days after the first administration or the previous administration.

Suitably the formulation is administered to ruminants. More preferably, the animal is a cow, goat or sheep.
Suitably the formulation is administered by subcutaneous or intramuscular injection. Upon administration, the formulation forms a depot.

  As used herein, the term “depot” refers to a reservoir of a formulation that remains at the site of administration and tends to release a retained therapeutic amount of selenomethionine so that absorption occurs over time. Point to.

  In a further aspect of the invention, the selenium status of an animal (e.g., in blood) compared to an untreated animal upon parenteral administration of a therapeutically effective amount of the formulation, such as a single dose or multiple doses, substantially as described above. It provides the use of a formulation in which the selenium concentration is increased 6-25 times over 95 days. This blood condition is safe and beneficial to animals and, in our experiments, is more than adequate to meet the essential requirements for animal growth and health.

  In addition, the inventors have shown that repeated administration of the formulation to dairy cattle increases the selenium concentration of milk by 27-54 times compared to untreated, and the concentration is more than doubled over 95 days. Found to be maintained. This enrichment is that up to 50% and 200% of the selenium RDI for adults and infants is provided by ingestion of 100 ml, respectively. This enrichment eliminates the need to add selenium during powder processing to powdered milk powder produced from milk and processed into infant formulas, as in current manufacturing methods.

  The selenium concentration in milk peaks between about 7-15 days after dosing and remains elevated compared to untreated over 95 days after dosing. The release rate of this depot was unexpected and was surprising to the inventors. This provides a useful time for the treated cattle to easily produce enriched milk (which can be collected as value-added special milk) and then return to normal production. Thus, the formulation provides a “switch” for switching milk selenium enrichment.

Furthermore, repeated administration of the formulation to sheep increases the concentration of selenium in the animal's muscle by a factor of 5-13 compared to untreated.
In our experiments, the injection of the formulation has a depot effect sufficient to allow a useful duration for the aforementioned response in the tissue (one or more of blood, milk and meat). As shown, the treated animals need not be kept for further processing after administration. One skilled in the art will recognize that the effect on the tissue can be titrated by administration to control the intensity and duration of the selenium response.

In our experiments, the relationship between selenium concentrations in whole blood or serum and milk or meat is proportional but not linear. This relationship varies depending on the selenium source used for animal assistance, and is different between selenomethionine and sodium selenate, and different between sodium selenate and sodium barium selenate. In our experiments, selenomethionine is the most effective adjuvant to enrich milk or meat selenium content relative to blood selenium concentration (Note 1).
Note 1: Knolls SO, Grace ND, Wurms K, Lee J, “The amount of dietary selenium versus blood, milk and casein selenium concentrations in grazing cattle And Significance of Forms (Non-of-dietary selenium on blood, milk, and casein selenium concentrations in i) p. 429-437.

  We have found that the formation of “extra” selenium species in milk, meat or both from treated animals is in the form of selenomethionine and selenocysteine, as free selenium ions and Se-methylselenocysteine. The amount is assumed to be small. Since the bioavailability and metabolic capacity of these forms of selenium is good, there is a possibility that it may be advantageous for consumers to spread the speciation of this nature.

Milk, meat, or both from treated animals can be obtained from the New Zealand Food Safety Agency (NZFS).
A: A group of New Zealand Food Safety Authority pesticides and veterinary medicines (Agricultural Compounds and Veterinary Medicines; ACVM) is considered safe for human consumption. Furthermore, in our experiments, treated lamb-derived meat is considered to be untreated meat as determined by a group of skilled taste evaluators and by surveys by a number of untrained consumer volunteers. In comparison, there was no change or decrease in flavor, aroma and other sensory characteristics.

  Here, four in livestock animals conducted to determine the effect of administration of the formulation on the blood selenium status, milk selenium concentration and (Examples 1, 4) or meat selenium concentration (Examples 2, 3) of the animals. In connection with the field test, the composition of the present invention will be described.

[Example 1: Selenium-enriched milk derived from dairy cattle]
A total of 13 grazing dairy cows (treated 6, untreated 7) were tested to determine the effect of the selenomethionine formulation over time on blood and milk selenium concentrations. Animals were treated by parenteral subcutaneous administration of the formulation, approximately as described above. The administration rate was about 0.35 mg / kg selenium / live weight. On days 1, 7, 17, 28, 45, 83 after administration, blood and milk samples were taken from the cows and analyzed for total selenium concentration.

  The results shown in FIG. 1 show a significant increase in mean blood selenium concentration 6-11 times over 83 days over untreated. The measurement was stopped at that time. As shown in FIG. 2, the milk selenium concentration increased significantly, showed a peak concentration 28 times that of the untreated about 7 days after administration, and the concentration remained elevated over 83 days after administration. .

  Clearly, a single selenomethionine injection in a dairy cow not only increases animal blood selenium concentration, but also increases selenium concentration in animal-derived milk, so the useful transfer of selenium from blood to milk Is demonstrated.

[Example 2: Selenium-enriched meat derived from lamb]
To determine the effect of the selenomethionine formulation over time on blood and muscle selenium concentrations, 60 young lambs in the grazing group were tested. On the first day of the study, the formulation was injected subcutaneously into 20 lambs about 4 weeks of age, approximately as described above. The dose rate was about 0.8 mg / kg selenium / live weight. The other 20 lambs were injected with a commercial formulation of barium selenate called Novartis Deposel. The administration rate was about 1.8 mg / kg selenium / live weight. An additional 20 lambs were untreated. On days 1, 19, 40, 89, and 138 after administration, blood samples were collected from lambs and analyzed for total selenium concentration and activity of glutathione peroxidase, a selenium-containing enzyme.

  Muscle samples were taken in a “serial slaughter” manner. In this manner, several animals from each treatment group were sacrificed at intervals until the last day of testing when all the remaining animals in the group were sacrificed. That is, muscle samples were collected from 2 animals per group on day 1 and 6 animals per group on days 40, 89, and 138, respectively. Two different muscles were analyzed per animal for selenium concentrations. The muscles were the semi-tendonoid muscle (m. Semi ofdinose; eye of round) and the triceps brachii (boler).

The results shown in FIG. 3 show that growth was impaired in untreated lambs lacking selenium. They did not grow to their full potential and lost weight as their health was compromised. In contrast, treatment with the selenomethionine formulation met the selenium requirements essential for lamb growth and health. In this regard, the effectiveness of this formulation as an animal adjunct was equivalent to Deposel, a well-known well-known animal therapeutic agent based on barium selenate (inorganic selenium salt).

  The results shown in FIG. 4 (upper panel) show that treatment with the selenomethionine formulation or Deposel resulted in a significant increase in mean blood selenium concentration over 138 days versus untreated. The measurement was stopped at that time. FIG. 4 (bottom panel) also shows that an alternative indicator of animal selenium status, ie, mean blood glutathione peroxidase activity, is significantly elevated by treatment.

  The results in FIG. 5 show how effective treatment with selenomethionine is over barium selenate to enrich meat selenium concentrations. Here, by administering a smaller amount on the first day (selenomethionine is 0.8 mg / kg selenium / live weight, barium selenate is selenium / live weight 1.8 mg / kg), A larger increase is occurring. The peak of increase was on day 40 (12 and 5 times greater than untreated). However, this maximum selenium concentration occurred when the lamb was still as small as 25 kg. On the 89th day, the live weight was 38 kg (weight that could be economically sacrificed), and the meat selenium concentration was reduced by 39% due to the diluting effect of the muscle obtained by the 13 kg growth. Regarding the abbreviations used in the legend of this figure, “SeMet” is selenomethionine, “BaSeO4” is barium selenate, “eye of round” is semi-tendonoid muscle, and “borer” is triceps.

  Obviously, a single selenomethionine injection in the lamb not only increases the selenium status of the animal, but also increases the selenium concentration in the animal's muscles, thus helping to facilitate the transfer of selenium from blood to muscle tissue Proven. Even at small doses (depot size), the selenomethionine formulation gives a pharmacokinetic profile similar to barium selenate (as shown by changes in blood selenium concentration over time). To obtain the maximum selenium concentration in the muscle, the formulation must be treated early in the life of the animal so that selenium is intrinsically incorporated into the muscle tissue of the rapidly growing animal.

Example 3: Lamb-derived selenium-enriched meat using an optimized treatment regime
To determine the time course effect of repeated treatments with selenomethionine formulations on blood and muscle selenium concentrations, 30 young lambs in the grazing group were tested. On the first day of the study, as described above, 16 lambs approximately 5 weeks of age were given a single subcutaneous injection of the formulation. The administration rate was about 0.7 mg / kg selenium / live weight. Of these, 10 received a second injection of the formulation on day 54. The administration rate was about 0.6 mg / kg selenium / live weight. Fourteen lambs were untreated throughout the study.

On days 1, 19, 54, 73, 90 after administration, blood samples were taken from lambs and analyzed for total selenium concentration (data not shown).
Muscle samples were taken in a shortened “serial slaughter” manner. In this manner, several animals from each treatment group were sacrificed at the beginning of the study before treatment, and all remaining animals in the group were sacrificed at the end of the study. That is, on the first day, muscle samples were collected from 5 untreated lambs. On day 95, samples were taken from the remaining 9 untreated lambs, 6 single injected lambs and 10 twice injected lambs. Two different muscles were analyzed per animal for selenium concentrations. The muscles were the semi-tendonoid (eye of round) and the longest back muscle (m. Longissimus dorsium lumborum; striploin).

The results in FIG. 6 show that lambs grow economically to a slaughterable weight with a first treatment with a selenomethionine formulation at a young age followed by a second injection of the formulation approximately 40 days prior to slaughter. Sometimes it shows how high selenium concentrations in muscle are maintained. The average live weight of lambs slaughtered on day 95 was 44 kg (data not shown). On that day, the meat selenium concentration was 13 times greater than untreated. As for the abbreviations used in the legend of this figure, “SeMet” is selenomethionine, “10 + 0” is a single injection lamb, “10 + 20” is a double injection lamb, “eye of round” is a semi-tendon-like muscle, “ “Strip loin” is the longest muscle of the back and back.

  The result of FIG. 7 shows the average response of a group of nine skilled sensory evaluators. Under controlled conditions, these respondents tasted cooked meat from 9 untreated lambs and 10 “10 + 20” (2 injections) lambs, and aromas according to an 8-point preference scale. Samples were compared for flavor, softness, texture, and semen. Treatment of lambs with selenomethionine formulations in an optimized manner had no effect on the edible quality or acceptability of the resulting selenium-enriched lamb.

[Example 4: Selenium-enriched milk derived from dairy cattle-repeated treatment]
Tested on a total of 40 dairy cows (randomly assigned to 4 groups of 10) to determine the effect of treatment time, including repeated treatment with selenomethionine formulation, on blood and milk selenium concentrations Went. The groups were: (a) untreated (“control” group), (b) selenomethionine (“single / low” group) at a dose rate of about 0.35 mg / kg selenium / live weight, (c) As described above, selenium / live weight about 0.35 mg / kg, then second similar injection on day 49 ("Repeated Low" group), (d) selenium / live weight about 0.70 mg / kg Then divided on day 49 into treatment consisting of a second similar injection ("Repeated High" group). On day 0, each group (n = 10 cows per group) received a single subcutaneous injection of the set treatment. Blood and whole milk samples were collected from cattle on days -9 and 0 before treatment, and also on days 5, 12, 26, 49, 54, 61, 76, and 95 during lactation. Details and timing of animal sampling are summarized in Table 1 below.

  The results shown in FIG. 8 show that blood selenium concentrations increased 10-18 fold in both single and repeated injection groups compared to the control group. The increase in blood selenium concentration in repeated treatments increased 9-20 times on day 54 compared to controls. The response to the second treatment was slightly less than the response to the first treatment, but the effect of the combination was cumulative. Overall, blood selenium concentrations remained very high during the study period (about 95 days).

In the results shown in FIG. 9, on the fifth day of the first sampling period, the selenium concentration in the whole milk shows a peak of 8 to 14 times that of the control. On day 54, with repeated treatments, milk selenium concentrations peaked 27-54 times greater than controls. Compared to the control, the milk selenium concentration was maintained approximately twice over 95 days. The response to the second treatment was slightly less than the response to the first treatment, but the effect of the combination was cumulative.

  We note that the peak concentration of milk after repeated administration represents a particularly effective extraction. We assume that the first administration prepares the mammary gland extraction process and the second selenomethionine injection is delivered to the milk at a higher rate.

  It will be appreciated from the above examples that formulations are provided that can increase and maintain selenium concentrations in one or more of animal blood, milk and meat over a period of time. Also provided are methods suitable for administration and preparation of this formulation.

2 is a graph showing the effect of a formulation that increases and maintains the selenium status of a treated “dairy cow” as indicated by blood selenium concentration throughout the field trial described in Example 1. FIG. n = about 6 per group. 2 is a graph showing the effect of a formulation that significantly increases the selenium concentration of untreated whole milk collected from “dairy cattle” throughout the field trial described in Example 1. FIG. n = about 6 per group. FIG. 5 is a graph showing the effect of a formulation that meets selenium nutritional requirements essential for growth and health in “slams” that are otherwise selenium-deficient, by animal weight throughout the field trial described in Example 2. FIG. n = 20 per group. The effect of the formulation to increase and maintain the selenium status of treated “lambs” as indicated by blood selenium concentration (upper panel) and blood selenoprotein glutathione peroxidase activity (lower panel) is demonstrated in Example 2. A set of graphs shown throughout the duration of the test. n = 20 per group. FIG. 3 is a graph showing the effect of a formulation to increase selenium concentration in untreated muscle from a treated “lamb” according to the field test described in Example 2. FIG. n = about 6 per group. FIG. 6 is a graph showing the effect of a formulation that increases selenium concentration in untreated muscle from treated “lambs” by field trials as described in Example 3. FIG. By making a second injection of the formulation 40 days before slaughter, the selenium effect is further increased. n = about 7 per group. The radar graph of the sensory attribute of the lamb by the field test as described in Example 3. No significant effect of selenomethionine treatment on the taste and texture of selenium-enriched meat has been shown. n = 6-10 per group. Increase and maintain the selenium status of the treated “dairy cow” as indicated by blood selenium concentration by making a single injection of the formulation or another injection about 50 days after the first injection The graph which shows the effect of a formulation through the period of the field test as described in Example 4. FIG. n = 10 per group. A formulation that increases the selenium concentration of untreated whole milk collected from “dairy cattle” by making a single injection of the formulation or another injection about 50 days after the first injection. The graph which shows an effect through the period of the field test as described in Example 4. FIG. n = 10 per group.

Claims (55)

  A formulation for parenteral administration comprising selenomethionine and one or more oil-based vehicles. The formulation according to claim 1, wherein the selenomethionine has a chemical structure of the following formula representing a D-form, an L-enantiomer or a racemic mixture thereof.

  The formulation according to claim 1 or 2, wherein the selenomethionine is a finely divided particle.   4. The formulation according to any one of claims 1 to 3, wherein the particle size distribution of selenomethionine is about 0.1 to 10 [mu] m.   The formulation according to any one of claims 1 to 4, wherein the concentration of selenomethionine is in the range of 25 to 100 g / L.   6. Formulation according to any one of the preceding claims, wherein the concentration of selenomethionine is about 50 g / L.   7. A formulation as claimed in any one of the preceding claims, wherein the one or more oil-based vehicles are non-allergenic, flow thinly at room temperature and are slow to degrade by oxidation.   8. A formulation according to any one of the preceding claims, wherein the oil-based vehicle has a viscosity of about 50-100 mPascal seconds at 23 ° C.   The formulation according to any one of claims 1 to 8, wherein the oil-based vehicle is vegetable oil.   10. Formulation according to any one of the preceding claims, wherein the oil-based vehicle is selected from peanut oil, poppy seed oil or walnut oil.   The formulation according to any one of claims 1 to 8, wherein the oil-based vehicle is an oil having a viscosity and temperature stability equal to peanut oil.   12. Formulation according to any one of the preceding claims comprising a suspending agent.   13. A formulation according to claim 12, wherein the suspending agent is beeswax.   14. A formulation according to claim 13, wherein the beeswax is bleached beeswax.   15. A formulation according to any one of claims 12 to 14 wherein beeswax is added at a concentration in the range of about 5-50 g / L.   16. A formulation according to any one of claims 12 to 15 wherein beeswax is added at a concentration of about 15 g / L.   17. A formulation according to any one of claims 12 to 16, wherein the suspending agent is pharmaceutical grade.   18. A formulation according to any one of claims 12 to 17, wherein sufficient suspending agent is added so that the density of the formulation is about 0.92 g / ml when measured at 23 ° C.   A method of increasing blood selenium concentration in an animal by parenteral administration of a formulation comprising selenomethionine and one or more oil-based vehicles.   A method of meeting selenium nutritional requirements for growth and health in deficient animals by parenteral administration of a formulation comprising selenomethionine and one or more oil-based vehicles.   A method of increasing selenium concentration in milk, meat or both of animal origin by parenteral administration of a formulation comprising selenomethionine and one or more oil-based vehicles.   A method of increasing selenium concentration in milk, meat or both of animal origin by repeated parenteral administration of a formulation comprising selenomethionine and one or more oil-based vehicles.   24. The method of claim 22, wherein the formulation is administered repeatedly at different intervals.   24. The method of claim 22 or 23, wherein the next administration of the formulation is performed about 50 days after the first or previous administration.   25. A method according to any one of claims 19 to 24, wherein the formulation causes the selenium concentration in the animal's milk to remain elevated for more than 90 days after administration.   26. A method according to any one of claims 19 to 25 wherein the formulation is administered to ruminants.   27. The method of claim 26, wherein the animal is a cow, goat or sheep.   27. A method according to any one of claims 19 to 26, wherein the formulation is administered by subcutaneous or intramuscular injection.   29. A method according to any one of claims 19 to 28, wherein the formulation forms a depot upon administration.   30. A method according to any one of claims 19 to 29, wherein the selenomethionine in the formulation is a finely divided particulate.   31. The method according to any one of claims 19 to 30, wherein the concentration of selenomethionine is in the range of 25 to 100 g / L.   32. A method according to any one of claims 19 to 31 wherein one or more oil-based vehicles in the formulation is non-allergenic, flows thinly at room temperature, and is slow to degrade by oxidation.   33. A method according to any one of claims 19 to 32, wherein the oil-based vehicle has a viscosity of about 50-100 mPascal seconds at 23 [deg.] C. 34. A method according to any one of claims 19 to 33, wherein the oil-based vehicle is selected from peanut oil, poppy seed oil or walnut oil.   35. A method according to any one of claims 19 to 34, wherein the formulation comprises a suspending agent.   36. The method of claim 35, wherein the suspending agent is beeswax.   37. A method according to claim 35 or 36, wherein the suspending agent is pharmaceutical grade.   38. A method according to any one of claims 35 to 37, wherein sufficient suspending agent is added to the formulation such that the density of the formulation is about 0.92 g / ml when measured at 23 ° C.   Use of a formulation comprising selenomethionine and one or more oil-based vehicles in the manufacture of a medicament for increasing the blood selenium concentration in an animal.   40. Use of the formulation according to claim 39, wherein the selenomethionine is a finely divided particulate.   41. Use of a formulation according to claim 39 or 40, wherein the concentration of selenomethionine is in the range of 25-100 g / L.   42. Use of a formulation according to any one of claims 39 to 41, wherein the one or more oil-based vehicles are non-allergenic, flow thinly at room temperature and are slow to degrade by oxidation.   43. Use of a formulation according to any one of claims 39 to 42, wherein the oil-based vehicle has a viscosity of about 50-100 mPascal seconds at 23 ° C.   44. Use of a formulation according to any one of claims 39 to 43, wherein the oil-based vehicle is selected from peanut oil, poppy seed oil or walnut oil.   45. Use of a formulation according to any one of claims 39 to 44 comprising a suspending agent.   46. Use of a formulation according to claim 45, wherein the suspending agent is beeswax.   47. Use of a formulation according to claim 45 or 46, wherein the suspending agent is pharmaceutical grade.   48. Use of a formulation according to any one of claims 45 to 47, wherein sufficient suspending agent is added so that the density of the formulation is about 0.92 g / ml when measured at 23 ° C.   49. Use of a formulation according to any one of claims 39 to 48 which increases the selenium status of the animal 6 to 25 times compared to an untreated animal.   49. Use of a formulation according to any one of claims 39 to 48, wherein the concentration of selenium in the muscle of the animal is increased 5 to 13 times compared to untreated.   49. Use of a formulation according to any one of claims 39 to 48, wherein the concentration of selenium in the animal's milk is increased 8-54 times compared to untreated.   49. The selenium concentration in an animal's milk is increased so that intake of 100 g provides up to 50% and 200% of selenium RDI for human adults and infants, respectively. Use of the formulation.   49. Use of a formulation according to any of claims 39 to 48, wherein the selenium concentration in the milk of the animal peaks between about 7 and 15 days after administration.   49. Use of a formulation according to any one of claims 39 to 48, wherein repeated administration increases milk selenium concentration by 27-54 fold compared to untreated.   49. Use of a formulation according to any one of claims 39 to 48, wherein repeated administration maintains the selenium concentration of milk more than doubled over 95 days.

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